tbuckley/cabot-search huggingface dataset:
Evaluation of studies with commonly used real world data sources submitted to ASCO journals: Initial steps toward furthering transparent reporting.
Authors: Benjamin Bates, Brooke Kania, Ashley Ketelhut, Sanjay Aneja
Journal: Journal of Clinical Oncology (2023)

6630 Background: Real world data (RWD) are used to understand treatment, care, and outcomes of patients with cancer. Reporting guidelines for observational studies, such as RECORD (health), RECORD-PE (treatment) and TRIPOD (prediction), were developed to increase the transparency of studies using RWD. These guidelines are not required for publication in ASCO Journals (JCO- Journal of Clinical Oncology, PO- Precision Oncology, OP- Oncology Practice, CCI- Clinical Cancer Informatics, GO- Global Oncology). Our objective was to describe the use of RWD among studies submitted to ASCO Journals and evaluate the applicability of guidelines and adherence to guidelines. Methods: ASCO submission system was used to identify all studies submitted to ASCO Journals between 2018-2022. Based on the abstract, the studies were categorized on whether selected RWD were used: SEER, Medicare, National Cancer Database [NCDB], Flatiron, CancerLinQ, IQVIA, Optum, MarketScan. Through manual review of the published manuscripts, we calculated positive predictive value (PPV) of our algorithm to identify the RWD. We estimated acceptance rate. For each study we evaluated the following: (1) linkages with other RWD; (2) applicability of reporting guidelines RECORD, RECORD-PE, TRIPOD; (3) use of flow diagram (RECORD) or study design figure for treatment and outcome assessment (RECORD-PE). Results: The PPV of our search algorithm was 79% (95%CI 73-84) but varied by journal (PPV 73-100; p=0.02). Based on our algorithm, among the 16,133 original reports submitted, 1,156 (7.2%) used one of the RWD sources. Overall acceptance rate among RWD sources was 18%. There was variability in submissions and acceptance rate of RWD by journal. OP and GO most and least frequently received a manuscript with the selected RWD 13% and 1%, respectively. GO accepted 77% of manuscripts that used selected RWD (88% of which were SEER). JCO accepted 3.5% of RWD manuscripts. Medicare, SEER, and NCDB were frequently identified data sources (61%, 31%, and 11%, respectively). SEER was linked to Medicare claims, surveys, or other sources in 77% of studies. The other data sources accounted for &lt;5% each, although submission of EHR-linked to claims/registry increased over time (OR 1.26: 95%CI 1.07-1.49). RECORD, RECORD-PE and TRIPOD were applicable to 100%, 10% and 8% of the studies. RECORD-PE and TRIPOD were most applicable to PO/OP/CCI and CCI, respectively. A flow diagram demonstrating selection of participants was present in 31% of the studies. A figure to visualize study design was used in &lt;5% of RECORD-PE relevant studies. Conclusions: RWD are commonly submitted and published within ASCO Journals. Reporting guidelines are applicable and particularly important when linkages occur. Studies using oncology RWD may benefit from reporting guidelines tailored to the unique qualities of these data sources and populations.
Neoadjuvant chemotherapy followed by definitive chemoradiation in technically unresectable oral cavity squamous cancers.
Authors: Mehak Trikha, Vijay Maruti Patil, Vanita Noronha, Nandini Sharrel Menon, Ajaykumar Chandrabhan Singh, Aditya Dhanawat, Pankaj Chaturvedi, Prathamesh S Pai, Devendra A Chaukar, Sarbani Ghosh Laskar, Kumar Prabash
Journal: Journal of Clinical Oncology (2023)

e18073 Background: Definitive Chemoradiation has dismal outcomes in very advanced oral cavity cancers. Surgical resection is the preferred modality of treatment . NACT followed by assessment for surgery is the standard algorithm used in technically unresectable oral cavity squamous cancers. Patients who are not amenable for surgery or not willing for the same are subjected to definitive Chemoradiation. There is very limited data about the outcomes of these patients and hence we have performed this analysis. Methods: This is an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable oral cavity squamous patients who received NACT. Adults patients with an eastern co-operative oncology group (ECOG) performance status (PS) 0-2 who were deemed as technically unresectable in a multi-disciplinary clinic (MDC) were included. These patients received 2-3 cycles of NACT (3-weekly) and underwent a response assessment. Depending on response and general condition, they were re-assessed in MDC and further therapy was decided. Patients who were not amenable to surgery and not willing for the and considered for definitive Chemoradiation were included in this analysis. Overall survival (OS) was calculated from date of diagnosis to date of death. Kaplan-meier method was used for estimation of 5 years OS. Impact of response to neoadjuvant chemotherapy on overall survival was calculated using log-rank method. Results: A total of 429 patients were analysed of which 387 (90.2%) were males The median age was 40 years (IQR; 40-54 years). The baseline ECOG PS was 0 in 163 (38%), 1 in 257 (59.9%) and 2 in 9 (2.1%) patients. The clinical stage at presentation was IVA in 257 (59.9%) patients and IVB in 172 (40.1%). The neoadjuvant regimen received were TPF regimen in 162 (37.8%) patients and two drug Taxane- Platinum regimen in the rest. The response rate to neoadjuvant therapy was 35.9% (N=154). Three thirty nine patients had an event with a median survival of 10 months (95%CI-;8.6-11.4). The five year survival was 15.6 % (Standard error 2%), while the 10 year OS was 9.6% (standard error 2.6%). On multivariate analysis, the only factor impacting the OS was response to neoadjuvant chemotherapy (HR: 0.54, 95% CI; 0.43-0.69; P=0.000). Conclusions: Neoadjuvant Chemotherapy followed by definitive Chemoradiation (who are not amenable for surgical resection or not willing) leads to dismal outcomes and further strategies to improve the outcomes are warranted.
Implementing liquid biopsy in rural cancer care when tissue is insufficient for molecular testing: Retrospective review.
Authors: Jaswinder Singh, Siraj Singh, Gina J. Singh, Amitoj Nagaich
Journal: Journal of Clinical Oncology (2023)

e15039 Background: Liquid biopsy is a promising and minimally invasive genetic test examining plasma circulating tumor DNA. Coupled with the rapidly developing next-generation sequencing (NGS) technologies, it holds the potential for implementation in selecting signal-matched therapeutic options. Analysis of tumor cell free DNA, or liquid biopsy, is emerging as a useful adjunct to tissue biopsies in advanced solid tumors. These tests may reduce the need for repeating invasive biopsies, and may be performed serially with minimal risk to patients. Many a times solid tumor biopsies are not sufficient enough to run next generation sequencing and hence the need for repeat biopsies. The purpose of our study is to document how liquid biopsies are being used in a large, diverse community based practice in rural Missouri where travel to tertiary care center for repeat biopsies is not easy and how often the results were able to demonstrate yield of finding FDA approved therapeutic options or clinical trials for these patients. Methods: A retrospective chart review was conducted on adult patients with advanced solid tumors whose tumors were not sufficient enough to be tested for next generation sequencing and hence tested with Guardant360 assay, between December 2015 and December 2022. A total of 515 patients were referred for testing by 4 oncologists from within a five satellite rural community cancer centers. Results: The majority of patients were tested upfront for molecular marker evaluation, in either newly diagnosed advanced cancer patients, or in recurrent patients without enough tissue for testing. 66 out of 515 patients (12.8 %) were not found to have any tumor alterations on liquid biopsy. A total of 16 histological types were tested among 449 patients with lung ( n = 177; (39.42% ),breast cancer ( n = 58; 12.9 %) and colorectal ( n = 135; 30 % ); cancers being the most common types of the 16 histological subtypes. Of those with positive test results (n = 449 ), 56 (12.4%) patients had ≥ 1 FDA approved, target-matched therapeutic opportunity. Similarly, 329 patients (73%) had ≥ 1 target-matched therapeutic opportunity, outside current indications. Lastly, when no FDA-approved target-matched therapy was available results from liquid biopsy testing offered signal-based clinical trial opportunity in all 449 patients. Conclusions: Implementation of NGS-based liquid biopsy testing is feasible within a community rural oncology practice. In the era of precision oncology, such assays have the potential to expedite the efforts towards target-matched therapies and signal-based clinical trial opportunities especially when there is problem of lack of accessibility and affordability of repeat biopsies is a problem.
Maintenance of castration with concomitant relugolix and apalutamide (Apa) in patients with high-risk localized prostate cancer (HR-LPC): 1 year update.
Authors: Gordon Brown, Laurence Belkoff, Jason Hafron, Pankaj Aggarwal, Rushikesh Potdar, Amitabha Bhaumik, Jennifer Phillips, Tracy McGowan, Neal D. Shore
Journal: Journal of Clinical Oncology (2023)

e17094 Background: Androgen deprivation therapy (ADT) is a mainstay in the management of prostate cancer (PC). We assessed the efficacy of achieving and maintaining castrate testosterone (T) levels when combining relugolix, an oral gonadotropin-releasing hormone antagonist, concomitantly with Apa, an androgen receptor inhibitor. The single-arm, open-label, multicenter, phase 2 Apa-RP study evaluates the biochemical recurrence-free rate in patients with HR-LPC following radical prostatectomy (RP) who received 12 months of adjuvant Apa and ADT (main study). A substudy was added to assess whether the approved maintenance dose of relugolix with concomitant Apa maintained castration. Study results of the 28-day coadministration of relugolix + Apa showed that all evaluable patients achieved and maintained castration at standard relugolix dose and were transitioned into the main study (Brown et al. Target Oncol. 2022). Herein, we report longer term data of T levels and safety findings in the substudy patients who received relugolix + Apa for 1 year. Methods: Patients (n = 12) with HR-LPC (PSA ≥20 ng/mL or Gleason score ≥8) received a loading dose of relugolix (360 mg) at substudy initiation (Day -14) followed by the standard, approved relugolix dose (120 mg/d) for 13 days. Starting on Day 1, patients received relugolix + Apa (240 mg/d) for 28 days, with substudy completion on Day 28. These patients transitioned to the main study and received relugolix + Apa for a total of 1 year. T levels (castrate level defined as &lt; 50 ng/dL) were measured at baseline (Day -14), Day 1, Day 28, and then every 3 months. Results: Of the 12 patients who continued onto the main study, 1 withdrew and another was noncompliant with therapy and subsequently withdrew but maintained castration while on therapy. Of the 10 patients who successfully completed therapy, 100% maintained castration during 1 year of concomitant therapy with relugolix + Apa . No patient required dose modification of relugolix. Median T level was 10.0 ng/dL after 1 year of treatment. One month after treatment discontinuation, 8/10 (80%) patients saw recovery of their T (T ≥50 ng/dL). Treatment-emergent adverse events (TEAEs) occurred in all 12 patients (100%). TEAEs were consistent with known safety profiles for each drug administered separately. Conclusions: During the 12 months of concomitant relugolix + Apa administration, all patients who completed therapy maintained castrate T levels without relugolix dose modification. All but 2 patients had T recovery within 30 days of therapy discontinuation. These data support long-term T suppression with relugolix + Apa at standard doses. Subsequent T levels will be reported upon final analysis of the main study. Clinical trial information: NCT04523207 .
A retrospective cohort study examining the effects of anti–PD-1 antibody in combination with apatinib in patients previously treated for HER2-negative advanced gastric/gastroesophageal junction cancer.
Authors: Xinfang Hou, Shuai Li, Chen Wu
Journal: Journal of Clinical Oncology (2023)

e16048 Background: Combining immune checkpoint inhibitors with vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors are effective in treating a number of solid tumors; however, evidence in advanced gastric/gastroesophageal junction (G/GEJ) cancer is limited. Methods: This retrospective study included consecutive patients who received a programmed cell death protein 1 (PD-1) inhibitor plus the VEGFR-2 inhibitor apatinib, second-line or later to treat unresectable advanced or metastatic, histologically-proven, human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer in a single center between November 1, 2018 and March 31, 2021. Treatment was continued until the disease progressed or the toxicity became intolerable. Results: Data from 52 patients (median age 64 years; 38 men) were analyzed. The primary tumor site was the stomach in 29 patients (56%) and the GEJ in 23 patients (44%). The number of previous line(s) of therapy was one in 22 patients (42%) and two or more in 30 patients (58%). Liver metastasis was present in 22 patients (42%) and 33 patients (63%) had two or more metastatic sites. PD-1 inhibitors taken included camrelizumab (n=28), sintilimab (n=18), pembrolizumab (n=3) and tislelizumab (n=1), all given 200 mg every 3 weeks (Q3W), and toripalimab (240 mg Q3W) and nivolumab (200 mg every 2 weeks) in 1 patient each. The objective response rate was 15.4% (95% confidence interval [CI] 6.9–28.1), the disease control rate was 61.5% (95% CI 47.0–74.7). After a median follow-up of 14.8 months (range 11.8–23.5), median progression-free survival was 4.2 months (95% CI 2.6–4.8), overall survival was 9.3 months (95% CI 7.9–12.9). Grade 3–4 treatment-related adverse events occurred in 12 patients (23.1%). There was no unexpected toxicity or death. Conclusions: Combination therapy with an anti-PD-1 antibody and apatinib was effective in patients with previously treated, unresectable advanced or metastatic G/GEJ cancer, with a manageable safety profile.
Regorafenib in patients (pts) with unresectable hepatocellular carcinoma (uHCC) in real-world practice in the United States (US): Final analysis of the prospective, observational REFINE study.
Authors: Ahmed Omar Kaseb, Roniel Cabrera, Renuka Iyer, Neehar Parikh, Richard Kalman, Kirhan Ozgurdal, Javeed Khan, Svetlana Babajanyan, Richard S. Finn
Journal: Journal of Clinical Oncology (2023)

e16114 Background: In the observational REFINE study of regorafenib (NCT03289273) in pts with uHCC, treatment-emergent adverse events (TEAEs) were consistent with those reported in the global, phase 3 RESORCE trial (YJ Kim, ILCA 2022). Median overall survival (OS) in the overall global cohort of REFINE was 13.2 months; here, we present the final analysis of the US pt cohort. Methods: REFINE was an international, prospective, multicenter study that enrolled pts with uHCC for whom a decision to treat with regorafenib was made by the treating physician prior to enrollment, according to the local health authority approved label. The primary objectives were safety, including incidence of TEAEs (MedDRA v25) and dose modifications due to TEAEs. Secondary endpoints included OS, progression-free survival (PFS), and duration of treatment (DoT). Results: Of the 1005 evaluable pts from the global cohort, 65 pts (6%) were from the USA. In the US cohort, 78% were male, 69% had ECOG PS 0/1, and the population was younger than the global cohort (54% were aged &lt;65 years vs 45% in the global cohort). The most common HCC etiology was hepatitis C in the US cohort (52% vs 24% in the global cohort) and the second most common was alcohol use (34% vs 25% in the global cohort). A lower proportion of US pts had extrahepatic spread compared with the global cohort (48% vs 59%), while a similar proportion had vascular invasion (both 34%). Use of prior immune checkpoint inhibitors was more frequent in US pts than in the overall global cohort (25% vs 10%). Most US pts (88%) had received prior sorafenib, consistent with the global cohort (96%). However, a relatively lower proportion of pts received regorafenib as a second-line therapy (71% vs 84% in the global cohort). Transarterial chemoembolization was the most common prior non-systemic treatment (42%). Median DoT was 3.1 months (range &lt;0.1–24.6 months) in US pts vs 3.7 months (range &lt;0.1–38.9 months) in the global cohort. TEAEs were reported in 91% of US pts and apart from a lower incidence of diarrhea and hand–foot skin reaction (HFSR) in US pts, incidences of TEAEs were comparable to the global cohort. In addition, TEAEs resulting in dose modification were relatively lower in US pts (38% vs 45% in the global cohort). Median OS in US pts was 11.4 months (95% CI 8.4, 18.0), similar to that reported for the global cohort (median OS 13.2 months [95% CI 11.6, 14.8]). Conclusions: The REFINE real-world study confirmed the safety and effectiveness of regorafenib in a broader population of pts than in the RESORCE trial. The findings remained consistent in US pts with uHCC. Clinical trial information: NCT03289273 . [Table: see text]
Diagnostic application of circulating CDH17 biomarker for screening GI malignancies.
Authors: Lui Ng, Deepak Iyer, Tony K Wong, Tsz Chun Hon, Stella Sun, John Moon Luk, Dominic Chi-Chung Foo
Journal: Journal of Clinical Oncology (2023)

3058 Background: Colorectal cancer (CRC) is the most common and treatable gastrointestinal (GI) cancer, yet it remains the second leading cause of cancer associated deaths globally. Cadherin-17 (CDH17) is a biomarker for GI cancers characterized by its overexpression in stomach, liver, and colorectal cancers but controlled expression in normal tissues from healthy adults. Although an improvement in the detection strategy of CDH17 is essential to apply it for large scale CRC screening. We have developed a novel diagnostic immunoassay using a panel of highly specific antibodies (PCT/US2019/032752) that unveiled CDH17 as a potential diagnostic maker with high detection sensitivity and specificity in CRC. Methods: The study recruited 150 patients (Retrospective specimens - 50 colorectal adenomas and 100 colorectal cancer) and 50 asymptomatic 18-80 years old blood donors (prospective specimens). CDH17 expression levels were measured within the individual blood-plasma samples using an enzyme-linked immunoassay. Results: The novel CDH17 diagnostic assay showed a wide operating dynamic range extending from 90ng to a lower limit of detection at 123pg. Using the assay, we observed a progressive and a significant increase in the plasma CDH17 concentration from the asymptomatic individuals to the colorectal adenoma group, while the CRC patients showed the highest expression of the circulating protein (median: 2.5ng/mL vs 4.5ng/mL vs 8.0ng/mL, P&lt;0.0001). Within the CRC group, a higher CDH17 expression was associated with advanced tumor invasion, occurrence of nodal or distant metastases, as well as a clinical presentation of an advanced stage disease. The diagnostic power of the assay in terms of ROC AUC values was higher than 0.9 with an overall sensitivity of 82% that extended to 100% for metastatic CRC, while the specificity was at 94% for all stages combined (P&lt;0.0001). Plasma CDH17 outperformed the clinically applied CEA and CA19-9 markers in differentiating the CRC patients from the asymptomatic population. Conclusions: The CDH17 immunoassay is potentially a diagnostics tool aid for the detection of CDH17 within blood samples prompting the early diagnosis of CRC. [Table: see text]
Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-US): NRG-GI008.
Authors: Arvind Dasari, Guan Yu, Scott Kopetz, Samuel A. Jacobs, Peter C. Lucas, Ibrahim Halil Sahin, Dustin A. Deming, Philip Agop Philip, Theodore S. Hong, Yesenia Rojas-Khalil, Jonathan M. Loree, Norman Wolmark, Greg Yothers, Thomas J. George, Christopher Hanyoung Lieu
Journal: Journal of Clinical Oncology (2023)

TPS3634 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage III A, B (all pts) and stage II, IIIC (ctDNA+ only) CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (SignateraTM, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP) + oxaliplatin (Ox) for 3-6 mos per established guidelines vs. serial ctDNA monitoring. Patients who are ctDNA+ post-operatively or with serial monitoring (Cohort B) will be randomized to FP+Ox vs. more intensive AC with addition of irinotecan (I) for 6 mos. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate vs. delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox vs FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022. NCT#: NCT05174169. Support: U10-CA-180868, -180822; UG1CA-189867; Natera, Inc. Clinical trial information: NCT05174169 .